Introduction: Diffusion-weighted MRI (DWI) can detect transient declines of the apparent diffusion coefficient (ADC) that represent spreading depression (SD) associated disturbances of the ion homeostasis and the concomitant extra- to intracellular water shift in the periinfarct tissue. We investigated the dynamics of the initial SD-related ADC transients in hyper- and normoglycemic rats after remote middle cerebral artery occlusion (MCAO) to test the hypothesis that an increased blood glucose level should result in a faster recovery of SD like transients in the periinfarct tissue. Methods: Six rats were rendered hyperglycemic by i.p. injection of streptozotocin 36 hours before induction of focal cerebral ischemia using the remote suture model. Periinfarct SD was monitored during the initial 15 minutes after remotely induced middle cerebral artery occlusion (MCAO) using serial ultrafast. Data for each ADC calculation was acquired in 16s. Perfusion imaging was performed immediately after the DWI using the same multi-slice EPI technique to follow a bolus injection of 0.3 mmol/kg Gd-DTPA. Multiple adjacent ROIs were defined in the ADC maps. The latency time from MCAO to the onset of the ADC decrease (LT), the time from the start of the ADC decrease to the maximal ADC decline (= T FADC), the time from the start of the ADC decrease to the ADC recovery and the maximal ADC change (F ADC) were defined in order to characterize the temporal evolution of the ADC. Results: The ischemic core in hyperglycemic rats had a significant prolongation of LT as compared to normoglycemic control rats. Furthermore, T FADC was significantly increased in the ischemic core of hyperglycemic rats. Transient ADC decreases during SD occurred in the periinfarct tissue of both experimental groups. Hyperglycemic rats showed a significantly faster recovery of transient ADC declines in ROIs 2 and 3 adjacent to the ischemic core (5.610.6 min. vs. 10.111.6 min. in controls, p=0.03). Tissue perfusion did not reveal significant differences between the two groups. Conclusion: We conclude that hyperglycemia delays the terminal depolarization in the ischemic core and supports a faster repolarization in severely mal-perfused pen-umbral tissue after SD, which reflects the increased availability of energy substrate in the state of hyper-glycemia.